Journal article

High-Efficiency Biocatalytic Conversion of Thebaine to Codeine

Xu Li, Konrad Krysiak-Baltyn, Luke Richards, Ailsa Jarrold, Geoffrey W Stevens, Tim Bowser, Robert E Speight, Sally L Gras

ACS Omega | American Chemical Society | Published : 2020


An enzymatic biosynthesis approach is described for codeine, the most widely used medicinal opiate, providing a more environmentally sustainable alternative to current chemical conversion, with yields and productivity compatible with industrial production. Escherichia coli strains were engineered to express key enzymes from poppy, including the recently discovered neopinone isomerase, producing codeine from thebaine. We show that compartmentalization of these enzymes in different cells is an effective strategy that allows active spatial and temporal control of reactions, increasing yield and volumetric productivity and reducing byproduct generation. Codeine is produced at a yield of 64% and ..

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Awarded by Australian Research Council Linkage Project scheme

Funding Acknowledgements

This work was supported by The Australian Research Council Linkage Project scheme (LP160100182) and Sun Pharmaceutical Industries Australia Pty Ltd.. We thank Dr Angela Bridges and her team at GSK, Stevenage, UK, for advice and provision of plasmids; The Bio21 Melbourne Mass Spectrometry and Proteomics platform and Melbourne Magnetic Resonance platform at The University of Melbourne for technical support; and Zongjia Chen, Garrick Spencer, and Dr Shuai Nie at The University of Melbourne for discussion and technical support.